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Biomedical subjects

A E Turco

Publications and source records attributed to A E Turco.

29 records · Page 2Linked to original sources
PubMed1995

Gene linkage analysis and DNA based detection of autosomal dominant polycystic kidney disease (ADPKD) in a newborn infant. Case report.

Bilateral polycystic kidneys were detected by ultrasound at 23 weeks gestation in a male fetus. Bilateral renal cysts were subsequently also found in the asymptomatic propositus' mother and grandmother, suggesting the diagnosis of autosomal dominant polycystic kidney disease (ADPKD). The renal ultrasonograms showed cortical cysts with normal or decreased-sized kidneys. Renal function was normal. Seven available members of the family were genotyped for flanking DNA markers tightly linked to the PKD1 gene on chromosome 16p, and for a polymorphism close to a second putative disease gene (PKD2) on chromosome 2. The genetic linkage approach allowed us to detect with a high degree of accuracy the ADPKD1 at risk chromosome in the three patients, as well as in a 28-year-old unaffected female. This report illustrates the feasibility and the usefulness of recent molecular genetic strategies for diagnostic purposes in ADPKD, especially when clinical and radiological data are atypical. Furthermore, it also confirms that early or very early onset forms of the disease are not uncommon, and should be considered in the differential diagnosis of childhood cystic disease.

Blotting, Southern↗
PubMed1993

Prenatal testing in a fetus at risk for autosomal dominant polycystic kidney disease and autosomal recessive junctional epidermolysis bullosa with pyloric atresia.

Amniocentesis and fetal skin biopsies were performed at 18 weeks of gestation in a fetus at risk for autosomal dominant polycystic kidney disease (ADPKD) and autosomal recessive junctional epidermolysis bullosa (EBJ) with pyloric atresia. A previous son of the couple under investigation had died at 3 months of EBJ. The mother of the propositus has ADPKD. Genetic linkage studies were carried out in 11 relatives (4 with ADPKD), and on fetal DNA obtained from cultured amniocytes, using 8 flanking DNA markers tightly linked to the PKD1 locus on chromosome 16p, and a DNA marker linked to another putative ADPKD locus on chromosome 2p. The linkage results indicated that the fetus had not inherited the ADPKD chromosome from the affected mother, with a diagnostic accuracy of > 99%. Ultrastructural and immunohistochemical analyses of multiple fetal skin biopsies showed no EBJ-associated abnormalities. Thus, combining recent morphological and molecular diagnostic methods, we could show that the fetus was free from both diseases. After 40 weeks of gestation, a normal male infant was delivered.

Adult↗
PubMed1993

Molecular genetic diagnosis of autosomal dominant polycystic kidney disease in a newborn with bilateral cystic kidneys detected prenatally and multiple skeletal malformations.

We report a case of an unusual prenatal presentation of polycystic kidneys associated with multiple skeletal limb defects, including polydactyly, syndactyly, bilateral agenesis of the tibia, and club foot. The ultrasonographic picture was consistent with a diagnosis of polycystic kidney disease, either the adult onset autosomal dominant type (ADPKD) or the early onset autosomal recessive form (ARPKD). However, there was a positive family history for ADPKD. Linkage analysis was performed in 10 family members, of whom four were affected, using six flanking DNA markers tightly linked to the PKD1 locus on chromosome 16p, and one marker linked to the putative PKD2 locus on chromosome 2p. Lod score determinations indicated that the affected gene in the family is most likely PKD1. The patient inherited the disease linked haplotype from his affected mother.

Adult↗
PubMed1992

Tracking disease genes by reverse genetics.

Increasingly, human genes are being identified by the "reverse genetics", or "positional cloning" approach. This molecular genetic strategy is particularly useful in mental illness, for which no readily detectable functional alterations are present to indicate candidate genes. The positional cloning procedure is briefly described. Significant examples of successful positional cloning are presented, including the fragile-X mental retardation syndrome gene. The study of gene expression may be complicated by genetic and non-genetic variability. Genomic imprinting may play a role in several mental illnesses, and may provide an explanation for the unusual inheritance pattern in fragile-X syndrome, for the phenotypic differences observed between Angelman and Prader-Willi syndromes, and for the juvenile onset form of Huntington disease. DNA instability may explain disease anticipation in fragile-X syndrome and myotonic dystrophy. Finally, the prospects of improvements in positional cloning methods for tracking genes responsible for mental illness are briefly discussed.

Chromosome Mapping↗
PubMed1991

High-density genetic and physical mapping of DNA markers near the X-linked Alport syndrome locus: definition and use of flanking polymorphic markers.

To refine the genetic and physical mapping of the locus for Alport syndrome (ATS), 22 X-chromosome restriction fragment length polymorphism (RFLP) markers that fall between Xq21.3 and Xq25 were tested for genetic linkage with the disease and also mapped with respect to a series of physical breakpoints in this region. The location of the COL4A5 gene, which has recently been shown to be mutated in at least some families with Alport syndrome, was determined with respect to the same physical breakpoints. Two large Utah kindreds were included in the genetic studies, kindreds P and C, with 125 and 63 potentially informative meioses, respectively. Both kindreds have essentially identical nephritis; however, kindred P has sensorineural hearing loss associated with the nephritis, while kindred C does not. A mutation in COL4A5 has been demonstrated for kindred P, but no change in this gene has yet been detected for kindred C. Twelve informative probes did not recombine with the disease locus in either kindred (theta = 0.0, with combined lod scores for the two kindreds ranging from 7.7 to 30.0). The closest markers that could be demonstrated to flank the disease locus were the same for each kindred and thus the locations of the mutations causing the two disease phenotypes are not distinguishable at the current level of genetic resolution. The flanking markers are also useful for the resolution of questionable diagnoses and allow accurate estimates for these families of the rate of sporadic hematuria in noncarrier females (7%) and the penetrance of hematuria for carrier females (93%).

Blotting, Southern↗
PubMed1990

Isolation, characterization, and physical localization of 33 human X-chromosome RFLP markers.

In a search for highly polymorphic X-specific loci, the X-chromosome DOE Ch35 phage library (LAOXNL01) was screened with three oligonucleotides representative of minisatellite consensus sequences. A total of 170 clones containing human inserts were isolated by hybridization to the oligonucleotide sequences; each was tested for polymorphism on five random female DNAs with six restriction enzymes. Among the 53 clones demonstrating a polymorphic pattern, 47 were of distinct origin. Twelve of the polymorphisms (23%) were determined to be autosomal. Polymorphisms for the remaining 35 clones were characterized, These polymorphisms represent 33 new X-chromosome RFLP loci, since two pairs of clones detected partially overlapping patterns. A pattern of similar length variation with multiple enzymes ("VNTR-type") was demonstrated in 6 (50%) of the 12 non-X-polymorphic clones. However, only 3 (9%) of the 33 X polymorphic loci showed VNTR-like patterns, suggesting a decreased amount of VNTR polymorphism on the X chromosome. The 33 polymorphic X loci were physically localized with a set of rodent x human somatic cell hybrid DNAs representing nine different X-chromosome breakpoints.

Base Sequence↗
PubMedDate not supplied

Autosomal dominant polycystic kidney disease: clinical and genetic aspects.

Autosomal dominant polycystic kidney disease (ADPKD) is an inherited systemic disease caused by at least three different genes. The renal and extrarenal clinical manifestations, and the systemic complications due to cystic and non-cystic abnormalities in ADPKD patients have been widely investigated. Cellular and molecular aspects of cystogenetic mechanisms concern epithelial tubular cell proliferation, remodelling of extracellular matrix, fluid secretion and accumulation, and relations between cell proliferation and apoptosis. In vitro studies on cystogenesis suggest a key role of cell-to-cell or cell-to-matrix interactions. Surface proteins mediating cell-to-cell contact, such as E-cadherin (polycystin?), integrin interactions, growth factors, receptor expression, are involved in the process of differentiation of the cellular condition and of the extracellular matrix. Blocking any one of these complex mechanisms should influence the orientation and polarization of epithelial tubular cells and should mediate the inversion of fluid secretion which ends in renal cystogenesis. ADPKD comprises at least three phenotypically indistinguishable but genetically distinct entities, caused by mutations in three autosomal genes: PKD1 (chromosome 16p13.3) is present in about 85% of patients; PKD2 (chromosome 4q13q23) in 10%; PKD3 (unknown chromosome) in a few families. PCR-based mutation detection methods, automated DNA sequencing, and other "functional" methods are used to screen and analyse ADPKD patients. It is not yet known whether the mutations identified so far in PKD1 and PKD2 inactivate the genes or generate an aberrant product. The products of PKD1 and PKD2 genes have been called polycystin 1 and 2. Polycystins are members of a family of interactive proteins involved in complex adhesive cell-cell, cell-matrix, protein-protein, and protein-carbohydrate interactions in the extracellular compartment, and are involved in the same pathway (ion channel regulator? ion channel? pore?) where mutations in only one of the simple genes (PKD3 too?) may cause the ADPKD phenotype. Genotype-phenotype correlations, in terms of disease severity and/or progression to end-stage renal disease, probably depend on other factors, both genetic and environmental (for instance: DD genotype of the ACE gene in ADPKD hypertensive patients), that might influence the clinical course and progression of ADPKD. The hypothesis of the "two hits" has been proposed to explain at the molecular level the focal nature of cyst formation.

Genetic Counseling↗